Over the past five years there has been a revolution in human genetics. The number of polymorphic markers available for linkage studies has risen dramatically from the 20-30 previously available to several hundred. These new markers have all been generated using recombinant DNA technology. the DNA markers have made it feasible to begin construction of a complete linkage map of the human genome. We are contributing to this effort by typing DNA markers in large reference pedigrees which are ideally structured to obtain a maximum of information on marker-marker linkages. The development of a human genetic linkage map will facilitate tremendously the localization of human genetic disease genes. It will also contribute significantly to improved diagnosis in these diseases and provide new avenues of investigation into the primary defects in many disorders. In the process of building the chromosomal linkage maps we expect to gain considerable information on basic genetic mechanisms in humans and to relate these to potential use of genetic linkage markers in diagnostic testing.